Anemia sideroblástica una enfermedad infrecuente de causas múltiples / Sideroblastic anemia, a rare disease of multiple causes

Introducción: La anemia sideroblástica es un trastorno hematológico que altera el proceso de la hematopoyesis, en la cual se ve afectada en mayor proporción la línea eritroide. Además, se presentan alteraciones en la síntesis del grupo hemo por disfunción mitocondrial en las células de la médula ósea. Objetivo: Indagar sobre la anemia sideroblástica, sus variables y los diferentes tipos de presentación que puede tener esta enfermedad. Métodos: Se llevó a cabo una revisión de la literatura en las bases de datos MEDLINE, EMBASE, Lilacs y ScienceDirect, con los descriptores: anemia sideroblástica, hematopoyesis, anomalías congénitas y 5-aminolevulinato sintetasa, en español e inglés. Se seleccionaron 26 artículos relacionados. Se hizo un análisis y resumen de la bibliografía revisada. Análisis y síntesis de la información: Es una enfermedad de origen congénito o secundario a otros procesos como el consumo de alcohol o inducido por algunos medicamentos. Se presenta con poca frecuencia y, en su mayoría, el diagnóstico se hace mediante estudios de laboratorio, como extendido de sangre periférica, estudio de médula ósea, a los que se les pueden aplicar diversas tinciones, realizar secuenciación o incluso realizar reacción en cadena de polimerasa. Conclusión: La anemia sideroblástica es una enfermedad puede relacionarse con otras alteraciones hematológicas que modifican el metabolismo del hierro. El tratamiento curativo es la trasfusión de hemocomponentes y debe hacerse un enfoque individualizado de cada paciente según el tipo de anemia sideroblástica(AU)

Introduction: Sideroblastic anemia is a hematological disorder that alters the hematopoiesis process. This condition affects, to a great extent, the erythroid line. In addition, alterations occur in the synthesis of the heme group due to mitochondrial dysfunction in the bone marrow cells. Objective: To investigate sideroblastic anemia, its variables and the different types of presentation of this disease. Methods: A literature review was carried out in the MEDLINE, EMBASE, Lilacs and ScienceDirect databases, using the descriptors anemia sideroblástica [sideroblastic anemia], hematopoyesis [hematopoiesis], anomalías congénitas [congenital anomalies] and 5-aminolevulinato sintetasa [5-aminolevulinate synthetase], in Spanish and English. Twety-six articles related to the topic were selected. An analysis and summary of the revised bibliography was carried out. Information analysis and synthesis: It is a disease of congenital origin or secondary to other processes such as alcohol consumption or induced by some medications. It occurs infrequently and its diagnosis is mostly made through laboratory studies, such as peripheral blood smear and bone marrow study, to which various stains can be applied, as well as sequencing or even polymerase chain reaction. Conclusion: Sideroblastic anemia is a disease that can be related to other hematological alterations that modify iron metabolism. The curative treatment is the transfusion of blood components. An individualized approach should be used according to the type of sideroblastic anemia(AU)

Clinical features and gene mutation spectrum in children with sideroblastic anemia / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features and gene mutation spectrum of children with sideroblastic anemia (SA) and the clinical value of targeted next-generation sequencing in the molecular diagnosis of children with SA.@*METHODS@#Clinical data were collected from 36 children with SA. Targeted next-generation sequencing was used to detect mutations in SA-related pathogenic genes and genes associated with heme synthesis and mitochondrial iron metabolism. The association between genotype and clinical phenotype was analyzed.@*RESULTS@#Of the 36 patients, 32 had congenital sideroblastic anemia (CSA) and 4 had myelodysplastic syndrome with ring sideroblasts (MDS-RS). Mutations in CSA-related genes were detected in 19 children (19/36, 53%), among whom 9 (47%) had ALAS2 mutation, 4 (21%) had SLC25A38 mutation, and 6 (32%) had mitochondrial fragment deletion. No pathogenic gene mutation was detected in 4 children with MDS-RS. Among the 19 mutations, 89% (17/19) were known mutations and 11% (2/19) were novel mutations. The novel mutation of the ALAS2 gene c.1153A>T(p.I385F) was rated as "possibly pathogenic" and the novel mutation of the SLC25A38 gene c.175C>T(p.Q59X) was rated as "pathogenic".@*CONCLUSIONS@#ALAS2 and SLC25A38 gene mutations are commonly seen in children with CSA, but mitochondrial gene fragment deletion also accounts for a relatively high proportion. For children with hypoplastic anemia occurring in infancy, mitochondrial disease should be considered.

Mutation Analysis of X-linked Sideroblastic Anemia in a 12-Month-Old Boy by Massively Parallel Sequencing

No abstract available.

Splicing factor SF3B1 mutations and ring sideroblasts in myelodysplastic syndromes: a Brazilian cohort screening study

ABSTRACT Background: Myelodysplastic syndromes (MDS) comprise a group of malignant clonal hematologic disorders characterized by ineffective hematopoiesis and propensity for progression to acute myeloid leukemia. Acquired mutations in the gene encoding RNA splicing factor 3B subunit 1 (SF3B1) are highly associated with the MDS subtypes presenting ring sideroblasts, and represent a specific nosological entity. The effects of these mutations on clinical outcomes are diverse and contrasting. Methods: A cohort of 91 Brazilian MDS patients, including patients with ring sideroblasts in the bone marrow, were screened for mutations in the SF3B1 hotspots (exons 12-15) by direct Sanger sequencing. Results: SF3B1 heterozygous mutations were identified in six patients (7%), all of them with ring sideroblasts, thus confirming the association between SF3B1 mutations and myelodysplastic syndrome subtypes bearing this morphologic feature (frequency of 6/13, p-value < 0.0001). Conclusion: This is the first screening of SF3B1 mutations in a cohort of Brazilian myelodysplastic syndrome patients. Our findings confirm that mutations in this splicing gene correlate with bone marrow ringed sideroblasts.

Congenital sideroblastic anemia-a new family with identification of K156E mutation of ALAS2 gene and literature review / 中华血液学杂志

<p><b>OBJECTIVE</b>To raise awareness of molecular pathogenesis and treatment of congenital sideroblastic anemia (CSA).</p><p><b>METHODS</b>A complete blood count and iron metabolism were detected from the proband and other members of the family. Mutation analysis was performed on the complete coding regions of ALAS2 gene by common polymerase chain reaction (PCR) using genomic DNA as a template from members the family. ALAS2 mutations were detected by direct sequencing and mutation types were confirmed by sequencing followed by plasmid cloning.</p><p><b>RESULTS</b>The proband male presented with microcytic hypochromic anemia (hemoglobin 84 g/L, mean corpuscular volume 64 fL, mean corpuscular hemoglobin 16.5 pg), and iron overload (serum iron 44.7 μmol/L, serum ferritin 3 123 μg/L and transferrin saturation 0.84). A mutation 466 A>G predicting a Lys156Glu amino acid change was identified in the proband and 3 females from the family. The proband was hemizygous for this mutation and presented with microcytic anemia and iron overload, while all 3 heterozygous females showed marginally increased red cell distribution width without any other symptoms. The proband treated with 300 mg of pyridoxine per day and iron chelation therapy with deferoxamine for one year had durable hematopoietic patients improvements, including increase in hemoglobin to 98 g/L and decrease in serum ferritin to 1 580 μg/L.</p><p><b>CONCLUSION</b>This was a novel K156E substitution in ALAS2 gene identified in a 3-generation pedigree in China. Our findings emphasized the importance of gene based diagnosis of CSA, and CSA patient with ALAS2 mutation responded to pyridoxine treatment.</p>

A Novel Hemizygous I418S Mutation in the ALAS2 Gene in a Young Korean Man with X-Linked Sideroblastic Anemia

No abstract available.

Gene mutation and myelodysplastic syndromes with ring sideroblast excess / 中国实验血液学杂志

Myelodysplastic syndromes (MDS) are heterogeneous clonal hematopoietic stem cell disorders with different mechanisms and diverse prognosis. The excess of ring sideroblasts (RS) is an important presentation MDS, but the mechanisms of RS appearance are obscure and the treatment of MDS-RS is intractable. Splicing factors play a very important role in the maturation process of eucaryon mRNA, recent studies indicate that there is a significant causal relationship between splicing factor 3B subunit 1 (SF3B1) mutation and the presence of ring sideroblasts. Lucubrating the downstream molecular of the mutated SF3B1 can facilitate exploring the mechanisms and new therapeutic strategies of MDS-RS.

Anemias sideroblásticas y puenteado basófilo: Indicador biológico por exposición ocupacional al plomo y sus derivados / Sideroblastic anemia and basophilic bridged: Biological indicator of occupational exposure to lead and its derivatives

En el presente estudio se evaluaron 34 individuos de ambos géneros (n = 15 mujeres y n = 19 hombres) con edades promedios de 37,35 ± 10,37. De los cuales 09 trabajadores de talleres mecánicos y 25 de imprentas gráficas con exposición laboral entre 8 a 10 horas/día. Bajo su consentimiento se les tomo muestra de sangre del antebrazo derecho para evaluar hematológica y morfológicamente glóbulos rojos (punteado basófilo), glóbulos blancos (segmentados neutrofilos), plaquetas y determinar por espectroscopia de absorción atómica con atomización elec trotérmica niveles séricos de plomo. Los resultados analíticos obtenidos para niveles de plomo globales expresados en μgL-1 de 36,03 ± 23,02 evidenciaron correlación directa y positiva con los parámetros bioquímicos evaluados. Ma yo res concentraciones de plomo en sangre coincidieron con pun teados basófilos toscos y alteraciones cualitativas morfológicas tales como hipocromía moderada en glóbulos rojos, granulaciones tóxicas e hipersegmentación en segmentados neutrofilos. No se observaron diferencias estadísticamente significativas con un p = 0,002 entre los grupos expuestos y tiempo de exposición por jornada laboral, más si entre los géneros con un p = 0,087, siendo más evidente el impacto de la exposición ocupacional en hombres, asumiendo mayor masa corporal y por ende mayor densidad ósea por donde este metal tóxico tiene un 95% de afinidad, además de contar el género masculino con mayor producción hematopoyética (La cantidad considerada normal fluctúa entre 4.500.000 (en la mujer) y 5.000.000 (en el hombre) por milímetro cúbico (o microlitro) de sangre). Los resultados obtenidos constituyen una herramienta útil para un pre-diagnóstico a exposición o intoxicación por plomo cuando por infraestructura no se cuente en laboratorios bioanalíticos con un equipo de espectroscopia de ab sorción atómica con atomización electrotérmica.

This study assessed 34 individuals of both genre (n = 15 women and n = 19 men) aged averages of 37.35 ± 10.37. Of whom 09 workers of garages and 25 printing graphs with occupational exposure between 8 to 10 hours per day. Under their consent took them right forearm blood sample to evaluate haematological and morphologically (stippling Basophilic) red blood cells, white blood cells (segmented neutrophils), pla te lets and by Atomic Spectrometry atomization absorption spectroscopy to determine serum levels of lead. The analytical re sults for overall lead levels ex pressed in μgL-1 36.03 ± 23.02 demonstrate positive and direct correlation with the biochemical parameters evaluated. High concentrations of lead in blood coincided with various crude basophiles and qualitative morphological alterations such as hypochromia moderate red globules, toxic granulation’s and hypersegmentation in segmented neutrophils. There were no statistically significant differences with p = 0.002 among exposed groups and exposure time by working day, more if genre with a p = 0.087, being most evi dent impact of occupational exposure in men, assuming greater mass body and therefore greater bone density where this toxic metal has a 95% of affinity’s well as the masculine gender with greater production hematopoietic (considered normal amount fluctuates between 4.500.000 (in women) and 5.000.000 (in humans) per cubic millimeter (microliter) of blood). The results constitute a useful tool for an prediag nostic to exposure or poisoning by lead when infrastructure don’t count in laboratories bioanalytic’s with a team of atomic absorption spectroscopy with spectrometry atomization.

Síndrome de Pearson: Reporte de un caso / Pearson syndrome: Case report

Entre las etiologías de anemias en la infancia, las citopatías mitocondriales son poco frecuentes. El síndrome de Pearson se diagnostica principalmente durante etapas iniciales de la vida y es caracterizado por anemia sideroblástica refractaria con vacuolización de células progenitoras en la médula ósea, disfunción del páncreas exocrino y variables alteraciones neurológicas, hepáticas, renales y endocrinas. En el siguiente informe reportamos un nuevo caso de lactante mayor femenino de 14 meses de edad, evaluada de forma multicéntrica con diagnostico clínico y molecular de síndrome de Pearson, con la deleción común de 4.977 pares de bases del ADN mitocondrial. Esta entidad ha sido asociada a diversos fenotipos dentro del amplio espectro clínico de las enfermedades mitocondriales.

Among the etiologies of anemia in the infancy, the mitochondrial cytopathies are infrequent. Pearson syndrome is diagnosed principally during the initial stages of life and it is characterized by refractory sideroblastic anemia with vacuolization of marrow progenitor cells, exocrine pancreatic dysfunction and variable neurologic, hepatic, renal and endocrine failures. We report the case of a 14 month-old girl evaluated by a multicentric study, with clinic and molecular diagnosis of Pearson syndrome, with the 4,977-base pair common deletion of mitochondrial DNA. This entity has been associated to diverse phenotypes within the broad clinical spectrum of mitochondrial disease.

Diagnóstico diferencial da deficiência de ferro: [revisão] / Differential diagnosis of iron deficiency: [review]

A deficiência de ferro é considerada a patologia hematológica mais prevalente no homem. Assim, é fundamental a adequada identificação de suas causas, bem como a diferenciação com outras patologias distintas para adequada abordagem da deficiência de ferro. Neste artigo são brevemente descritas outras condições que podem cursar com anemia microcítica, tais como: talassemias, anemia de doença crônica, anemia sideroblástica e envenenamento por chumbo, patologias estas que devem ser afastadas durante investigação de anemia ferropriva.

Iron deficiency is considered to be the commonest hematological pathology in humans. Thus, the essential steps in an adequate approach of iron deficiency include: the proper identification of its causes and the differentiation between iron deficiency and other conditions. This article briefly describes other conditions that may present with microcytic anemia such as thalassemia, anemia of chronic diseases, sideroblastic anemia and lead intoxication. These diseases should be considered during the investigation of iron deficiency anemia.

Clinical and biological features in refractory anemia with ringed sideroblasts with fluctuant platelet counts / 中国实验血液学杂志

The objective of this study was to explore the differences between refractory anemia with ringed sideroblast (RARS) and RARS associated with marked thrombocytosis (RARS-T) in the clinical, biological features and prognosis. The morphological changes of cells were observed by bone marrow smear and biopsy. Immunologic phenotype was analyzed by flow cytometry, and chromosome was examined by conventional chromosomal analysis. JAK2 V617F and MPL W515L mutations were screened by allele-specific polymerase chain reaction (AS-PCR) and sequence analysis. The results showed that this case was clinically diagnosed as RARS with thrombophilia, the level of serum potassium was positively related with platelet counts. When platelets increased, the clusters of atypical giant platelets and megakaryocytes were observed in peripheral blood and bone marrow examined by bone marrow smear and bone marrow biopsy respectively, JAK2 V617F and MPL W515L mutations were negative. It is concluded that RARS may transform into RARS-T accompanied with megakaryocyte proliferation, large atypical platelets and negative JAK2 V617F. Preventing thrombophilia and monitoring relative gene mutations are necessary when atypical giant platelets and fluctuant platelet counts occurred in process of RARS with tendency to RARS-T.

A case of sideroblastic anemia caused by lead-containing herbal medication / 대한내과학회지

Although lead intoxication is commonly mentioned as a cause of sideroblastic anemia, no well-documented case exists in the literature. We encountered a patient with sideroblastic anemia caused by lead-containing herbal medicine. A 34-year-old woman was admitted to our hospital with abdominal pain. She had taken herbal medicine for her general health. Anemia, hyperbilirubinemia, and elevated lactic dehydrogenase were found from the laboratory data. Bone marrow biopsy showed pathological ringed sideroblasts. Her serum level of lead was high and the lead content of the tablet was higher than permitted. We diagnosed her with sideroblastic anemia secondary to lead poisoning caused by herbal medicine. We stopped her from taking herbal medicine and she gradually recovered from anemia.

Identification of a Hemizygous R170H Mutation in the ALAS2 Gene in a Young Male Patient with X-linked Sideroblastic Anemia / 대한혈액학회지

X-linked sideroblastic anemia (XLSA) is a rare hereditary disease characterized by microcytic hypochromic anemia, ineffective erythropoiesis and the presence of numerous ringed sideroblasts in the bone marrow. The causative gene is the erythroid delta-aminolaevulinate synthase 2 gene (ALAS2) on Xp11.21. We report here a case of XLSA. The patient was a 20-year-old Korean man referred to our hospital under the impression of sideroblastic anemia (SA). Laboratory findings, including a peripheral blood smearand bone marrow study, were compatible with SA. The family history was not remarkable. Based on the early age of onset, we suspected a hereditary form of SA, particularly XLSA. Direct DNA sequencing of ALAS2 detected a hemizygous c.509G>A (R170H) mutation in exon 5 of the gene. The patient showed minimal response to pyridoxine treatment. To the best of our knowledge, this is the first case of genetically confirmed XLSA from a mutation in ALAS2 in Korea.

Relationship between mitochondrial DNA and myelodysplastic syndromes - review / 中国实验血液学杂志

Mitochondria is the main place of biological oxidation and energy transform. Mitochondrial DNA encodes the complex of respiratory chain in mitochondria and its mutation can cause a series of human disease. Mitochondrial DNA mutation which observed in myelodysplastic syndrome (MDS) patients cause the MDS by the mechanism of iron metabolism disorder, gene instability and hemopoietic progenitor cell apoptosis. In this review the characteristics of mitochondrial DNA structure, the mitochondrial DNA mutation and the possible mechanism of mitochondrial DNA mutation in pathogenesis of MDS were summarized.

Mlasa syndrome: a case report

Mitochondrial myopathy, lactic acidosis, and siderobiastic anemia [MLASA] syndrome is a rare autosomal recessive disorder of oxidative phosphorylation and iron metabolism. The association between myopathy and siderobiastic anemia was initially reported in 1974. Here we report an 8.5 year old boy with normal cognitive function, suffering from chronic progressive weakness in his lower extremities, inability to walk and palor, Microcytic siderobiastic anemia, mild lactic acidosis and inflammatory myopathy [myositis] in muscle biopsy was detected and treated; the response to corticosteroid therapy and rehabilitation was excellent and the patient was ambulatory after four months